Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), remodel extracellular matrix under physiological and pathological conditions and are implicated in pathogenesis of cardiovascular diseases, cancer and in chronic inflammation. We have endeavoured to assess whether concentrations of MMPs, TIMPs, and anti-inflammatory adiponectin are altered by pharmacological treatment of acute thyrotoxicosis or by radioiodine therapy (RIT). Material and methods We measured serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, and adiponectin, TSH, free T 4 (FT 4 ) and free T 3 (FT 3 ) in 15 patients (4 males), age (years) 51.8±15.3 (mean±SD) with hyperthyroidism treated with thiamazole (Group 1) and in 20 subjects (2 males), treated for thyrotoxicosis with radioiodine, age 52.3±12.4 (Group 2), where blood samples were taken before RIT, visit 1 (V1), seven days post RIT, visit 2 (V2), and two to three months post RIT, visit 3 (V3). Results In Group 1 there was no significant change in concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2 or adiponectin, despite a fall in FT 4 and FT 3 (8.74±4.79 pg/ml vs 3.54±2.40 pg/ml, for FT 3 , and 4.48 ±2.21 ng/ml vs 1.02±1.07 ng/ml, for FT 4 , p<0.001). In Group 2 RIT did not cause any acute change in serum MMP-2, MMP-9, TIMP-1 and TIMP-2 or adiponectin (V1 vs V2). However, there was a significant increase in serum adiponectin [from 15201±8860 ng/ml (V1) to 19373±8657 ng/ml (at V3), p<0.05], and TIMP-2 at V3 [from 129±45 ng/ml (V1) to 149±38 ng/ml (V3), p<0.01]. There was no significant change MMP-2, MMP-9 and TIMP-1 between V1 and V3. There was a decrease in FT 4 and FT 3 from 24.4±15.4 pmol/l (V1) to 14.7±10.6 pmol/l (V3), and from 10.0±5.65 (V1) to 6.1±4.8 pmol/l (V2), p<0.01, for FT 4 and FT 3 , respectively. Conclusions Radioiodine therapy of thyrotoxicosis does not alter serum MMP-2, MMP-9 or TIMP-1 concentrations either acutely or after about three months of observation. An increase in serum adiponectin might reflect favourable effects of radioiodine administration on cardiovascular risk factors, while an increase in TIMP-2 (principal MMP-2 inhibitor) might lead to a decrease in free MMP-2 concentrations.
R E S E A R C HOpen Access In contrast to matrix metalloproteinases, serum adiponectin concentrations increase after radioiodine treatment of thyrotoxicosis 1* 21 12 A LewińA Brona , KC Lewandowski , E Skowroski ,ńskaJóźwiak andA Milewicz
Abstract Background:Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), remodel extracellular matrix under physiological and pathological conditions and are implicated in pathogenesis of cardiovascular diseases, cancer and in chronic inflammation. We have endeavoured to assess whether concentrations of MMPs, TIMPs, and antiinflammatory adiponectin are altered by pharmacological treatment of acute thyrotoxicosis or by radioiodine therapy (RIT). Material and methods:We measured serum concentrations of MMP2, MMP9, TIMP1, TIMP2, and adiponectin, TSH, free T4(FT4) and free T3(FT3) in 15 patients (4 males), age (years) 51.8±15.3 (mean±SD) with hyperthyroidism treated with thiamazole (Group 1) and in 20 subjects (2 males), treated for thyrotoxicosis with radioiodine, age 52.3±12.4 (Group 2), where blood samples were taken before RIT, visit 1 (V1), seven days post RIT, visit 2 (V2), and two to three months post RIT, visit 3 (V3). Results:In Group 1 there was no significant change in concentrations of MMP2, MMP9, TIMP1, TIMP2 or adiponectin, despite a fall in FT4and FT3(8.74±4.79 pg/ml vs 3.54±2.40 pg/ml, for FT3, and 4.48 ±2.21 ng/ml vs 1.02±1.07 ng/ml, for FT4, p<0.001). In Group 2 RIT did not cause any acute change in serum MMP2, MMP9, TIMP1 and TIMP2 or adiponectin (V1 vs V2). However, there was a significant increase in serum adiponectin [from 15201 ±8860 ng/ml (V1) to 19373±8657 ng/ml (at V3), p<0.05], and TIMP2 at V3 [from 129±45 ng/ml (V1) to 149±38 ng/ ml (V3), p<0.01]. There was no significant change MMP2, MMP9 and TIMP1 between V1 and V3. There was a decrease in FT4and FT3from 24.4±15.4 pmol/l (V1) to 14.7±10.6 pmol/l (V3), and from 10.0±5.65 (V1) to 6.1±4.8 pmol/l (V2), p<0.01, for FT4and FT3, respectively. Conclusions:Radioiodine therapy of thyrotoxicosis does not alter serum MMP2, MMP9 or TIMP1 concentrations either acutely or after about three months of observation. An increase in serum adiponectin might reflect favourable effects of radioiodine administration on cardiovascular risk factors, while an increase in TIMP2 (principal MMP2 inhibitor) might lead to a decrease in free MMP2 concentrations. Keywords:Matrix metalloproteinases, Adiponectin, Thyrotoxicosis, Radioactive iodine
Introduction The term matrix metalloproteinases (MMPs) refers to a group of enzymes that remodel extracellular matrix in various physiological and pathological conditions, such as neoplasms, inflammatory and cardiovascular diseases [1]. In particular, increased activity of MMPs in blood
* Correspondence: alewin@csk.umed.lodz.pl 1 Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Rzgowska St. No. 281/289, 93338 Lodz, Poland Full list of author information is available at the end of the article
vessels has been implicated in formation of aneurysms [2], as well as in formation of unstable atherosclerotic plaques, in turn, leading to an increased risk of throm botic and embolic events, including myocardial infarc tions and strokes [35]. Adiponectin is an abundant plasma protein secreted from adipocytes. It has been thought to be a key mol ecule in the development of type 2 diabetes mellitus and metabolic syndrome, which are epidemiological targets for preventing cardiovascular disease. In addition to